Nature Microbiology最新文献

{"title":"Finishing the fight against HIV","authors":"","doi":"10.1038/s41564-026-02510-4","DOIUrl":"10.1038/s41564-026-02510-4","url":null,"abstract":"Despite major advances in HIV therapies and access to care, an HIV vaccine or cure strategy has yet to be realized. To achieve these goals, more support for collaborative research is needed.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 10","pages":"2667-2668"},"PeriodicalIF":18.7,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-026-02510-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oncogenic viral infection triggers LAMP2A SUMOylation and chaperone-mediated autophagy to promote tumorigenesis","authors":"Yulin Zhang, Zhongwei Dong, Xiaoting Chen, Ke Peng, Qingye Huang, Wutian Rao, Shu Song, Liming Zhang, Shujun Gao, Caixia Zhu, Yuyan Wang, Erle Robertson, Zhenghong Yuan, Fang Wei, Qiliang Cai","doi":"10.1038/s41564-026-02476-3","DOIUrl":"10.1038/s41564-026-02476-3","url":null,"abstract":"Chaperone-mediated autophagy (CMA) is a critical regulator of cancer progression and antiviral responses, often modulated by post-translational modifications. SUMOylation, a reversible post-translational modification, is implicated in viral infection and tumorigenesis, yet its role in CMA regulation remains unclear. Here we demonstrate that oncogenic viruses hijack CMA by inducing nuclear localization and SUMOylation of lysosomal-associated membrane protein 2A (LAMP2A), a central lysosomal receptor. Specifically, tripartite motif containing 32 (TRIM32) mediates SUMO2/3 conjugation to LAMP2A at lysine residues K104, K132 and K289. Using Kaposi’s sarcoma-associated herpesvirus as a model, we found that TRIM32-induced LAMP2A SUMOylation activates CMA, thereby promoting viral persistence, tumour growth and angiogenesis in vivo. Importantly, TRIM32 expression positively correlates with LAMP2A in tumour tissues from patients with Kaposi’s sarcoma-associated herpesvirus-, Epstein–Barr virus- and human papillomavirus-associated cancers, and peptide inhibitors targeting SUMOylated LAMP2A demonstrate potent antitumour and antiviral efficacy in vitro and in mice. Together, our findings position LAMP2A as a promising druggable target for treating virus-associated cancers. TRIM32-mediated SUMOylation of LAMP2A triggers classical chaperone-mediated autophagy, which viruses hijack to drive tumour growth. Peptide blockers of this modification show antitumour activity in mice model, identifying LAMP2A as a viable target.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 10","pages":"2883-2900"},"PeriodicalIF":18.7,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phylogeny-agnostic strain-level prediction of phage–host interactions from genomes using machine learning","authors":"Avery J. C. Noonan, Lucas Moriniere, Edwin O. Rivera-López, Krish Patel, Melina Pena, Madeline Svab, Alexey Kazakov, Adam Deutschbauer, Edward G. Dudley, Vivek K. Mutalik, Adam P. Arkin","doi":"10.1038/s41564-026-02482-5","DOIUrl":"10.1038/s41564-026-02482-5","url":null,"abstract":"Bacteriophages offer promising alternatives to antibiotics for treating drug-resistant infections and engineering microbiomes, but applications are limited by challenges related to selection of phages infecting specific bacterial strains. Here we present a phylogeny-agnostic machine-learning framework predicting strain-level phage–host interactions across diverse bacterial genera from genome sequences alone. Systematically optimizing the workflow over 13.2 million training runs across six datasets (115,037 interactions, 949 bacterial strains, 518 phages), we achieved performance matching species-specific methods (AUROC 0.67–0.94) while eliminating phylogenetic constraints. Experimental validation of 1,240 predicted E. coli phage–host interactions confirmed generalizability (AUROC 0.84), while genome-wide RB-TnSeq screens verified that 68.6% of experimentally identified infection mediators were captured computationally. Model-guided cocktail design achieved up to 97.5% bacterial coverage with five phages, and up to a 3.1-fold improvement in single-phage selection over promiscuity-based selection. This platform enables rational phage-therapy design and precision microbiome engineering with applications across clinical, agricultural and industrial contexts. This platform identifies phages capable of infecting specific bacterial strains using genome sequences alone and could enable rational phage-therapy design and precision microbiome engineering.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 10","pages":"2778-2793"},"PeriodicalIF":18.7,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-026-02482-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prophylactic treatment with broadly neutralizing antibody VRC01 selects for escape mutants after infection in Antibody-Mediated Prevention trials","authors":"Carolyn Williamson, Lyle Curry, Nonhlanhla N. Mkhize, Elena E. Giorgi, Craig A. Magaret, Bronwen E. Lambson, Sinethemba Bhebhe, Haajira Kaldine, Thandeka Moyo-Gwete, Morgane Rolland, Raabya Rossenkhan, Nina Marie G. Garcia, Chivonne Moodley, Anna Yssel, Yunda Huang, Alaine A. Marsden, Daniel B. Reeves, Bryan T. Mayer, Roger E. Bumgarner, Nicolas Beaume, Dylan H. Westfall, Michal Juraska, Allan C. DeCamp, Hugh Murrell, Hongjun Bai, Wenjie Deng, Alec P. Pankow, Tanmoy Bhattacharya, Talita York, Nonkululeko Ndabambi, Lennie Chen, Hong Zhao, Asanda Gwashu-Nyangiri, Ruwayhida Thebus, Paula Cohen, Ben Murrell, Shelly Karuna, John Hural, Nyaradzo Mgodi, Srilatha Edupuganti, Lynn Morris, David Montefiori, M. Juliana McElrath, Myron S. Cohen, Lawrence Corey, Paul T. Edlefsen, Peter B. Gilbert, Penny L. Moore, James I. Mullins","doi":"10.1038/s41564-026-02467-4","DOIUrl":"10.1038/s41564-026-02467-4","url":null,"abstract":"Broadly neutralizing antibodies (bnAbs) show promise in HIV prevention, yet viral escape remains a challenge. In the Antibody-Mediated Prevention (AMP) trials, the CD4 binding site (CD4bs) bnAb VRC01 blocked acquisition by VRC01-sensitive strains. However, its influence on viral evolution post acquisition is not fully understood. Here we analysed 11,730 HIV envelope sequences generated during the AMP trials from 47 participants, identifying VRC01-mediated de novo escape mutations in 8 of 26 VRC01-treated participants but none in 21 placebo participants. These mutations were found at very low frequencies (<1%) in globally circulating viruses, suggesting that they may confer fitness costs. Escape mutations, primarily located in the Loop-D and β23/V5 regions of Env, conferred cross-resistance to several CD4bs bnAbs; however, more potent CD4bs bnAbs such as N6 and 1–18 largely retained their activity. Our findings demonstrate that prophylactic VRC01 can select for viral escape after infection, underscoring the need for next-generation bnAbs with improved breadth and potency to enhance durability and efficacy of antibody-based HIV prevention. Prophylactic bnAb VRC01 selected for escape mutations in 31% of HIV breakthrough infections, but these mutations were rare in circulating viruses suggesting a fitness cost. More potent bnAbs such as N6 and 1-18 largely retained activity against escape variants.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 10","pages":"2694-2706"},"PeriodicalIF":18.7,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-026-02467-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149075477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Convergent receptor use at the coronavirus One Health interface","authors":"Christine Tait-Burkard","doi":"10.1038/s41564-026-02491-4","DOIUrl":"10.1038/s41564-026-02491-4","url":null,"abstract":"Two independent studies identified host species-specific aminopeptidase N as the entry receptor for hedgehog merbecoviruses, revealing convergent receptor use with alphacoronaviruses, but through a distinct binding site. Defining barriers to receptor use across species could help predict future host jumps and emerging transmission risks at the wildlife–veterinary–human interface.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 10","pages":"2680-2682"},"PeriodicalIF":18.7,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149075517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systematic mapping of bacteriophage gene essentiality with HIDEN-SEQ","authors":"Dorentina Humolli, Damien Piel, Jessica Ransome, Kathrin Bausch, Sarah Tschudin-Sutter, Monica Ortelli, Christoph Dehio, Jan-Willem Veening, Alexander Harms","doi":"10.1038/s41564-026-02455-8","DOIUrl":"10.1038/s41564-026-02455-8","url":null,"abstract":"The arms race of bacteriophages and their bacterial hosts has inspired major breakthroughs in biotechnology and shaped phages as fierce predators with great clinical potential to fight multidrug-resistant bacterial pathogens. However, the large amount of genes of unknown function in phage genomes remains a major obstacle for the molecular understanding of phage–host interactions. Here we present HIDEN-SEQ (hidden Acr-enabled transposon-insertion sequencing), a transposon-insertion sequencing method for phages that systematically links viral genes to selectable phenotypes. Using model phage T4, we show that HIDEN-SEQ readily reproduces the gene essentiality map established over decades of research. Our method is easily portable across diverse non-model phages and reveals conditionally essential genes in multiple bacterial hosts and growth conditions, including previously unknown antidefence factors that we matched to specific antiviral defences. We anticipate that HIDEN-SEQ will be leveraged to reveal functions of viral genes with direct relevance for microbial ecology, biotechnology and phage therapy. HIDEN-SEQ (hidden Acr-enabled transposon-insertion sequencing) is a transposon-insertion sequencing method for phages that systematically links their genes to selectable phenotypes.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 10","pages":"2751-2763"},"PeriodicalIF":18.7,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-026-02455-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149049508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Defining the essential genome of diverse phages with phage Tn-seq","authors":"Natalie Kyte, Manuela Fuchs, Leah M. Smith, Peter C. Fineran","doi":"10.1038/s41564-026-02486-1","DOIUrl":"10.1038/s41564-026-02486-1","url":null,"abstract":"Phages are important drivers of bacterial evolution and have potential as antimicrobials. However, incomplete understanding of phage biology and our inability to rapidly engineer them with new genetic cargo hinder progress towards phage-based therapies. Here we develop an unbiased, genome-wide mutational tool for phages. This approach, phage Tn-seq, uses Tn5 transposon mutagenesis using anti-CRISPR-based selection and deep-sequencing. Phage Tn-seq was successful across diverse phages, including a nucleus-forming jumbo phage and enabled gene essentiality assignment consistent with phage structural proteomics and core gene conservation. In addition, insertion biases allowed prediction of transcriptional direction and early injected and highly expressed regions. We exploit transposons to deliver new cargo to phages within a few days and created an orthogonal artificial intelligence-designed Acr transposon system to generate phage double mutants. Transposon insertion was also achieved in phages with hypermodified DNA. Phage Tn-seq is a versatile tool to advance our understanding and application of phages. Phage Tn-seq uses Tn5 transposon mutagenesis with anti-CRISPR-based selection and deep sequencing as a method to generate unbiased, genome-wide mutations across diverse phages","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 10","pages":"2764-2777"},"PeriodicalIF":18.7,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149049509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pseudomonas aeruginosa induces the generation of pathogenic IFNγ⁺Th17 cells that promote lung damage and chronic inflammation in cystic fibrosis.","authors":"Irene Dusetti, Gianmarco Conte, Matteo Chiara, Simone Puccio, Daniela Guidone, Eugenia Ricciardelli, Javier Cibella, Mirko Ronzio, Diletta Dolfini, Elio Rossi, Paolo Landini, Miriam Ascagni, Riccardo Orlandi, Francesco Damarco, Alessandro Palleschi, Andrea Gramegna, Francesco Blasi, Enrico Lugli, Luis J Galietta, Søren Molin, Helle K Johansen, Clelia Peano, Moira Paroni","doi":"10.1038/s41564-026-02469-2","DOIUrl":"https://doi.org/10.1038/s41564-026-02469-2","url":null,"abstract":"<p><p>Cystic fibrosis (CF) involves cycles of bacterial infection and sustained inflammation. IFNγ⁺Th17 cells are implicated in chronic inflammation, yet their role in CF remains undefined. Here we identify two pathogenic Th17 subsets, Th1/17⁺ and pro-inflammatory Th17 (pTh17) cells, selectively enriched in CF lungs colonized by Pseudomonas aeruginosa. These pathogenic subsets derive from protective conventional Th17 (cTh17) precursors and, following activation, directly disrupt pulmonary epithelial integrity and trigger exaggerated inflammatory responses. Transcriptomic and T cell receptor profiling reveal in situ reprogramming and clonal selection of Th1/17⁺ and pTh17 cells in CF lungs. Mechanistically, clinical P. aeruginosa strains persist within dendritic cells and induce a polarizing IL-1β/IL-23 cytokine axis that promotes IFNγ⁺Th17 differentiation over classical Th1 lineage commitment. P. aeruginosa early isolates, lacking chronic adaptation signatures, still potently reprogramme cTh17 cells, inducing a transcriptional programme that mirrors CF lung-resident Th1/17⁺ and pTh17 profiles. These findings show that P. aeruginosa subverts mucosal immunity and establishes a self-sustaining immunopathological loop, offering potential targets for CF precision therapies.</p>","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":" ","pages":""},"PeriodicalIF":18.7,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149039954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sequential gene loss promotes expansion of monophasic Salmonella Typhimurium ST34.","authors":"Xiaolei Wu, Teng Wang, Chenghao Jia, Haiyang Zhou, Yan Li, Stephen Baker, Min Yue","doi":"10.1038/s41564-026-02483-4","DOIUrl":"https://doi.org/10.1038/s41564-026-02483-4","url":null,"abstract":"<p><p>Understanding the genetic factors facilitating emergence of infectious diseases is critical, however, mechanisms underlying expansion of pathogenic bacterial variants remain unclear. Here we performed a large-scale genomic analysis of 44,597 Salmonella Typhimurium genomes and observe that sequential gene loss in monophasic Salmonella Typhimurium (mSTM) ST34 explains its clonal expansion as an increasingly prevalent zoonotic lineage. Functional and in vivo competition experiments show that a frameshift mutation in dinB, a polymerase for translesion DNA synthesis, leads to transcriptional changes affecting flagellin gene expression and subsequent loss of the flagellin-encoding fljB, altering the requirements for gut infection. Temporal evolutionary modelling supports a role for gene loss events in a specific chronological order for mSTM ST34 expansion. Our findings reveal a stepwise pathoadaptation model underpinning clonal global spread, providing mechanistic insights relevant to forecasting future pandemics.</p>","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":" ","pages":""},"PeriodicalIF":18.7,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148990749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vivo CRISPRi screens reveal Escherichia coli functional adaptations in the mouse gut","authors":"Amandine Maire,&nbsp;Monica Ortelli,&nbsp;Emma Tkacz,&nbsp;Christoph Dehio,&nbsp;Benoit Chassaing,&nbsp;Harry Sokol,&nbsp;Nathalie Rolhion,&nbsp;David Bikard","doi":"10.1038/s41564-026-02471-8","DOIUrl":"10.1038/s41564-026-02471-8","url":null,"abstract":"Escherichia coli exhibits remarkable genetic diversity that enables it to adapt to the intestinal environment. Here we establish an in vivo CRISPR interference platform that leverages bacterial gene fitness as a high-resolution functional reporter of E. coli adaptations within mice harbouring a defined minimal microbial community (OligoMM12). The screen revealed that diet profoundly shapes the metabolic landscape of E. coli and the essential gene profile identified cross-feeding interactions. Comparison between a laboratory strain (MG1655), a uropathogenic strain (CFT073) and an adherent-invasive E. coli (AIEC LF82) identified distinct genetic requirements for intestinal colonization, highlighting divergent motility, stress response and respiration strategies. In a host inflammatory environment, we found that AIEC LF82 preferably colonized the small intestine with a mobile genetic element, Gally prophage, playing an important role in modulating fitness. These findings provide a high-resolution genetic atlas of E. coli’s functional adaptation and demonstrate the utility of functional genomics to probe the gut environment itself. In vivo silencing of genes in E. coli strains using CRISPRi reveals specific genetic factors and metabolic adaptations that influence colonization in the mouse gut under variable physiological conditions.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 10","pages":"2911-2924"},"PeriodicalIF":18.7,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148990732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}